Outcomes of Outpatient Versus Inpatient Induction of Labor: A Systematic Review and Meta-Analysis

Induction of labor (IOL) has become a common practice in obstetrics, leading to an increase in antenatal admissions and workload. This review aims to explore the available options for outpatient IOL and their effectiveness. We conducted an electronic search for trials on Cochrane, PubMed, Google Scholar, and Web of Science databases for randomized control trials (RCTs) comparing inpatient and outpatient labor induction and covering the period until 2024. We selected randomized trials that compared IOL in outpatient vs. inpatient settings and involved mechanical or hormonal agents. The participants were pregnant women with singleton fetuses who were more than 37 weeks and low risk for IOL with a Bishop score <6. When comparing outpatient and inpatient induction methods, we found no significant differences in cesarean section rates and vaginal delivery. Outpatient induction generally resulted in shorter hospital stays. Using a Foley catheter for outpatient induction reduced the cesarean section rate and total hospital stay. There were no safety concerns with this approach. IOL in this analysis was shown to be similar to inpatient IOL in most of the measured outcomes. Implementation of IOL in an outpatient setting proved to be safe with similar outcomes to inpatient IOL.


Introduction And Background
Induction of labour is a common daily obstetric practice that currently places a significant workload on obstetric units, especially with the rising number of inductions.Numerous studies have tested the concept of outpatient induction of labour as a method that may reduce this burden and increase satisfaction among women and staff without compromising patient safety or obstetric and neonatal outcomes [1].
In outpatient settings, labour induction may involve the use of mechanical devices such as a single or double balloon Foley catheter, osmotic Hegar dilators like (DILPAN-S), or hormonal techniques such as prostaglandin gel or inserts, mifepristone, and misoprostol.Most modern obstetric units that use mechanical methods and perform labour induction in an outpatient setting typically work with low-risk patients and use these methods primarily when the overall clinical risk is low.Prostaglandin inserts, on the other hand, have been the subject of multiple studies and have been shown to be beneficial for outpatient induction of labour (IOL), particularly in high-income nations where prompt follow-ups and interventions are guaranteed.
To investigate the efficacy and safety of outpatient induction compared to inpatient IOL, we compiled all relevant randomized controlled trials (RCTs) into a meta-analysis and we performed a subgroup analysis comparing outpatient versus inpatient induction using a Foley catheter.Our updated review aims to support decisions regarding the use of outpatient IOL by examining the effects of mechanical and hormonal agents and general obstetric and neonatal outcomes.

Materials And Methods:
This meta-analysis was conducted following the PRISMA guidelines and the protocol for systematic reviews and meta-analyses in 2020.There were no major amendments made to the protocol, except for the addition of a single secondary outcome, which was the total duration of oxytocin use.
Inclusion Criteria: We rigorously focused on randomized control trials (RCTs) comparing outpatient and inpatient induction of labour.Additionally, we considered studies that examined outpatient versus outpatient induction of labour using various agents.Exclusion criteria were Inpatient RCTs without outpatient comparison, Induction of high-risk pregnant population, and Outpatient induction with other methods which still under research like Isosorbide mononitrate, and Non-RCT designs.
There were six studies from USA, Four from Australia, Four from Canada and Malaysia, and 1 study from Finland, NewZealand, Russia and Portugal.All studies reported their source of funds which is not commercial, but Antonio F et al [19], reported the source of funds from Medicem company which is the supplier of hygroscopic dilator (DILPAN-S), though the authors declared no conflict of interest.Also, all studies declared no conflict of interest except for Anthony C. Sciscione et al [9], Ryan G. et al [13], and Stitely et al [17], who didn't comment on it.
Outcomes extracted from studies included broad clinical obstetric outcomes, primarily Caesarean section rate, operative vaginal delivery, and vaginal delivery rate.Neonatal outcomes mainly focused on special care baby unit (SCBU) admission.Secondary outcomes include SCBU admission, maternal satisfaction, induction to amniotomy Interval, Induction to delivery Interval, use of oxytocin, intrapartum fever, Induction to SROM, tachysystole and, operative vaginal delivery, total hospital stay, Vaginal delivery within 24 hours.

Search Methods for Identification of Studies:
Electronic Searches We started the search for relevant articles on platforms such as Cochrane and local electronic libraries.We then extended our search to include MEDLINE, EMBASE, and CINAHL.Additionally, we manually searched other platforms like BMC, the European Journal, and the American Journal for any relevant studies.After screening the titles and abstracts, we searched for protocols and full articles.Any articles that were not freely available were accessed through our local Health Service Executive (HSE) library in Ireland. Figure (1) shows the flow diagram for screening and selecting the studies and Table (1) shows the characteristics of included studies.

TABLE 1: Characteristics of included studies
Three researchers, MM, MB, and FA, conducted a manual electronic search for studies using keywords related to outpatient induction of labour.The keywords included phrases such as "outpatient induction of labour," "mechanical outpatient induction of labour," "outpatient versus inpatient induction of labour," "outpatient induction of labour with Foley catheter," "outpatient IOL with an osmotic hegar's dilator," "induction of labour," and "home induction of labour."After the studies were gathered, they were screened by reviewing the titles and abstracts to check if they met the previously established inclusion criteria.There were no restrictions on countries or languages when searching for the studies.
Data was extracted from selected studies and entered manually into RevMan web, as prior identified interventions were already prepared, intervention from each study Outcomes were reported as summary risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) Selection of studies.The data was analyzed using the RevMan web, and the results were presented as forest plots.Dichotomous data were shown as risk ratios and continuous data were presented as mean differences.If significant heterogeneity was observed, a random effect model was used.Additionally, SPSS version 29 was utilized to aggregate demographic data from all studies, including age and parity.
Risk of bias assessment in included studies was conducted by Two independent authors for each selected study.Both authors reviewed the full text of the studies and utilized the ROB2 tool to assess the study's validity.This involved examining all 5 domains of ROB2, including the randomization process, allocation sequence, assessment of baseline imbalance, performance bias, outcome bias, missing data, and selective reporting.Any disagreements were resolved through discussion and by referencing the Cochrane Handbook.
In some cases, a third or fourth author was consulted, and on one occasion, we sought guidance from a professor at the University of Galway, Ireland."Disputes arise regarding the fact that most studies are not blinded.This could reduce the validity of the study and increase the risk of bias.If there are no obvious deviations from the intended intervention, it should not increase the risk of bias.Furthermore, if a deviation is detected, we try to understand its potential impact, and as a result, the risk of bias will either be high or of some concern.We follow the ROB 2 questions and domains in detail to assess the risk of bias for each study." in detail to assess the risk of bias for each study.

Risk of bias in included studies:
The risk of bias was assessed according to the ROB2 tool summary of assessment in Figure (2) and Figure (3).The majority of included studies were assessed to be at low risk for bias with the randomization process, Two studies were assessed with unclear risk Ryan G. et al [13], and Wilkinson et al [8].Most of the studies mentioned the process for allocation.The studies assessed were with unclear or high risk include Anjanique et al [16], Anthony C. Sciscione et al [9], Elizabeth et al [3], Haavisto et al [4], Policiano et al [7], Rahana Abdul Rahman et al [10], Ryan G. et al [13], Wilkinson et al [12], and Wise et al [15].The included studies in this analysis were all open-labelled and not blinded.As a result, most of them were assessed to be at high risk, according to the ROB2 tool for non-blinded studies.When using the ROB2 tool, checking for any deviation from the intended intervention is important.Therefore, we assessed studies with clear or no deviation from the intended intervention to have an unclear risk of bias.For the attrition bias, Ten studies were assessed to be at low risk of bias.Four studies with unclear risk Anthony C. Sciscione 2001 [9], Beckmann 2020 [2], Ryan G. et al [13], and Wilkinson et al [12] And two studies were judged to be at high risk of attrition bias Policiano et al [7], and Wilkinson et al [8].Most of the studies were assessed to be at low risk for selective reporting.
Reporting bias assessment: We Investigated reporting bias using funnel plots for the primary and secondary outcomes.No publication bias was observed in the Funnel plot (symmetrical) for the main outcome as shown in (Figures 4-7).Other secondary outcomes showed asymmetry, which indicate presence of reporting bias and subsequently downgraded as an evidence.Statistical heterogeneity was measured using I2, and interpreted according to Cochrane guidelines as follows: 0% to 40% might not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; 75% to 100% represents considerable heterogeneity.With significant heterogeneity we used random effect methods, additionally, we investigated sensitivity within forest plots.Sensitivity analysis was performed with the exclusion of studies with a high risk of bias where possible.The GRADE approach was used to assess the certainty of the evidence.

Result Of Main analysis, Outpatient versus Inpatient Induction Of labour (all methods combined):
A total of 18 randomized control trials, with 4886 patients, compared outpatient to inpatient induction using all available methods of induction either mechanical or hormonal.The mean age for the outpatient group was 29.3 and the mean age for the inpatient group was 29.2.

Primary Outcomes:
There was no difference in Caesarean section rate between outpatient versus inpatient induction (4421 patients, 16 RCT), RR 1.01 [0.90, 1.14] Moderate certainty of evidence (Figure 8).Also, no difference in Operative vaginal delivery (3803 patients, 13 RCT), RR 1.12(0.98 to 1.30) moderate certainty of evidence (figure 9), and no difference in vaginal delivery rate (2914 patients, 10 RCT ) observed as well (figure 10), RR 1.08(0.94 to 1.24) Low certainty of evidence as shown in the GRADE approach summary in Table ( 2) and (3).Demonstration of the analysis is shown in the forest plot in Figures (8)(9)(10)(11).*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).CI: confidence interval; MD: mean difference; RR: risk ratio GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.Subgroup Analysis Involved the Following:

Comparison of outpatient induction with Foley catheter versus inpatient induction with Foley catheter:
There is a reduction in Caesarean section rate in outpatient Induction with Foley catheter compared to inpatient RR 0.74 (056-0.99),(744, 7 RCT ), and Induction to delivery interval (hours): MD *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).CI: confidence interval; MD: mean difference; RR: risk ratio GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).CI: confidence interval; MD: mean difference; RR: risk ratio GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.The interval from induction to delivery interval was observed to be little increase in outpatient IOL with Foley catheter versus inpatient with Prostaglandins, MD 1. *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).CI: confidence interval; MD: mean difference; RR: risk ratio GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.In this review, 18 randomized controlled trials (RCTs) were included, involving 4886 patients, to compare the induction of labour in outpatient and inpatient settings using different methods.As expected, there was Clinical heterogeneity between the selected studies, so subgroup analysis was performed to compare the same induction methods used in outpatient versus inpatient settings.Regarding the main outcomes, there was no difference in the rates of cesarean section, operative vaginal delivery, and vaginal delivery between outpatient and inpatient induction, regardless of the method used.No differences were observed in other perinatal, labour and delivery, or neonatal outcomes.However, it was noted that outpatient induction resulted in a shorter interval from induction to the onset of labour, as well as a shorter interval from admission to delivery.Additionally, the outpatient group had a shorter hospital stay.These findings suggested that outpatient induction is a safe option for reducing hospital stays in low-risk women undergoing induction of labour.It is important to note that, no major morbidities were mentioned in the included studies, and there was no difference in febrile morbidities between the outpatient and inpatient groups.Dong et al. reported similar findings of no difference in perinatal, labour, and neonatal outcomes, as well as shorter hospital stays with outpatient induction compared to inpatient induction in their systematic reviews [1,41,42,43].They concluded that outpatient induction can be safely conducted in selected populations.Furthermore, when comparing outpatient and inpatient induction with a Foley catheter, a reduced rate of cesarean section, shorter intervals from induction to delivery, and decreased total hospital stay was observed (low certainty of evidence) without affecting labour or neonatal outcomes [1,44,45].When comparing inpatient induction with Prostaglandin to outpatient induction, subgroup analysis revealed no significant differences in reported outcomes (very low certainty of evidence).The only notable difference was in hospital stay duration, which was shorter for the outpatient group.Zarco et al reported similar findings [41], as did Mazzoli et al in their systematic review [42].However, Mazzoli et al noted a slight increase in rates of uterine hyperstimulation in the outpatient group, unlike our findings.We attribute this discrepancy to the low number and quality of studies included, which were insufficient to draw conclusions.Furthermore, Mazzoli et al included two out of three studies with retrospective cohorts, and the overall quality of the studies was too weak to reach a definitive conclusion.In the last subgroup analysis between outpatient foley catheter induction and inpatient induction with hormonal methods, no difference was demonstrated between the methods in caesarean section rate and special care baby unit admission (SCBU), the interval from induction to delivery however slightly increased in outpatient foley catheter group.
We recommend further studies comparing outpatient induction with various methods, as there is a lack of research in this area.Alfirevic [41], suggested using cohort study designs for this comparison, as it would provide more information about patient perspective and effectiveness compared to randomized trials where blinding is not possible, which lowers the strength of evidence.

Fetal
mode of birth, induction to delivery interval, vaginal delivery within 24 hours of commencement of cervical More than 18 years, Gestational age more than 37 weeks, Unsuitable for outpatient IOL, not suitable for hormonal induction, Bishop score more additional use of prostaglandin E2 and/or mechanical methods for cervical ripening; additional use of oxytocin; the interval from cervical ripening start to labour onset; labour duration; operative delivery rate; and the total hospital length of stay Age more than 18year, singleton fetus,

FIGURE 12 :FIGURE 13 :FIGURE 14 :FIGURE 15 :
FIGURE 12: Secondary Outcome Forest Plots: Interval from induction to labour onset, Interval from admission to delivery and oxytocin usage, Main analysis, Outpatient versus Inpatient Induction of labour.
2. Comparison of outpatient versus inpatient induction with prostaglandins (Gel or insert);There is little reduction in total hospital stay in outpatient compared to inpatient induction with prostaglandin, MD 1.96 lower(2.55 lower to 1.37 lower) (figure19).

TABLE 5 : Subgroup Analysis Outpatient Versus Inpatient Induction With Hormonal Methods; FIGURE 19: Subgroup Analysis; Total Hospital Stay (Hours); Outpatient versus Inpatient Induction with Hormonal methods:
3. Comparison of outpatient induction with Foley catheter versus inpatient induction with Prostaglandins: